Sensor platform using a non-horizontally oriented nanotube element

ABSTRACT

Sensor platforms and methods of making them are described. A platform having a non-horizontally oriented sensor element comprising one or more nanostructures such as nanotubes is described. Under certain embodiments, a sensor element has or is made to have an affinity for an analyte. Under certain embodiments, such a sensor element comprises one or more pristine nanotubes. Under certain embodiments, the sensor element comprises derivatized or functionalized nanotubes. Under certain embodiments, a sensor is made by providing a support structure; providing one or more nanotubes on the structure to provide material for a sensor element; and providing circuitry to electrically sense the sensor element&#39;s electrical characterization. Under certain embodiments, the sensor element comprises pre-derivatized or pre-functionalized nanotubes. Under other embodiments, sensor material is derivatized or functionalized after provision on the structure or after patterning. Under certain embodiments, a large-scale array of sensor platforms includes a plurality of sensor elements.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of the following application, thecontents of which are incorporated herein in their entirety byreference:

Sensor Platform Using a Non-Horizontally Oriented Nanotube Element (U.S.patent Ser. No. 10/844,883) filed May 12, 2004., which claims priorityto and the benefit of the filing dates of the following:

-   -   Horizontally Oriented Sensor Constructed with Nanotube        Technology (U.S. Provisional Pat. Appl., Ser. No. 60/470,410),        filed May 14, 2003;    -   Vertically Oriented Sensor Constructed with Nanotube Technology        (U.S. Provisional Pat. Appl., Ser. No. 60/470,371), filed May        14, 2003; and    -   Resistance and Capacitance Modulation Structures Constructed        with Nanotube Technology (U.S. Provisional Pat. Appl., Ser. No.        60/501,143), filed Sep. 8, 2003.

The following are assigned to the assignee of this application, and arehereby incorporated by reference in their entirety:

-   -   Nanotube Films and Articles (U.S. Pat. No. 6,706,402), filed        Apr. 23, 2002;    -   Electromechanical Memory Array Using Nanotube Ribbons and Method        for Making Same (U.S. Pat. No. 6,919,592), filed on Jul. 25,        2001;    -   Electromechanical Three-Trace Junction Devices (U.S. Pat. No.        6,911,682), filed on Dec. 28, 2001;    -   Methods of Making Carbon Nanotube Films, Layers, Fabrics,        Ribbons, Elements and Articles (U.S. patent application Ser. No.        10/341,005), filed on Jan. 13, 2003;    -   Electro-Mechanical Switches and Memory Cells Using        Vertically-Disposed Nanofabric Articles and Methods of Making        the Same (U.S. Provisional Pat. Appl., Ser. No. 60/446,786)        filed on Feb. 12, 2003;    -   Electro-Mechanical Switches and Memory Cells Using        Horizontally-Disposed Nanofabric Articles and Methods of Making        the Same (U.S. Provisional Pat. Appl., Ser. No. 60/446,783),        filed on Feb. 12, 2003;    -   Patterning of Nanoscopic Articles (U.S. Provisional Pat. Appl.        Ser. No. 60/501,033), filed on Sep. 8, 2003;    -   Patterning of Nanoscopic Articles (U.S. Provisional Pat. Appl.        Ser. No. 60/503,099), filed on Sep. 15, 2003;    -   Non-Volatile Electromechanical Field Effect Transistors and        Methods of Forming Same (U.S. Provisional Pat. Appl. Ser. No.        60/476,976), filed on Jun. 9, 2003; and    -   Sensor Platform Using a Horizontally Oriented Nanotube Element        (U.S. patent application Ser. No. 10/844,913) filed on May 12,        2004.

BACKGROUND

1. Technical Field

The present application relates generally to methods for the detectionof target analytes and for measuring or detecting various electricalvalues by utilizing individual nanosensors and nanosensor arrays, andthe application more particularly relates to means or platforms forcreating such sensors and sensor arrays.

2. Discussion of Related Art

Chemical sensors and biosensors have been utilized for detecting manyspecies, from contaminants in air (e.g., in air quality sensors) to thepresence of particular DNA segments in blood samples or other samples.More recently, chemical and biosensors utilizing nanotubes, such assingle-walled carbon nanotubes (SWNTs) have been proposed. Such sensorstake advantage of the smaller size and greater sensitivity of thesensor. See, e.g., J. Kong et al., Science, vol. 287, pp. 622-625 (Jan.28, 2000).

Chemical sensors made of nanotubes may be functionalized or otherwisemodified to become molecule-specific or species-specific sensors, see P.Qi et al., “Toward Large Arrays of Multiplex Functionalized CarbonNanotube Sensors for Highly Sensitive and Selective MolecularDetection,” Nano Lett., vol. 3, no. 3, pp. 347-51 (2003); Dai et al.,“Carbon Nanotube Sensing,” U.S. patent application Ser. No. 10/175,026,filed on Jun. 18, 2002. On the other hand, such sensors may comprisenon-functionalized semiconducting tubes and may sense for the presenceof known chemicals, see, e.g., Kong, supra.

Because it is difficult to control the placement of individual nanotubesbetween electrodes, the reliable fabrication of nanoscale sensors usingindividual nanotubes is problematic. In addition, the nanotubes so usedare singular. Thus, devices using them may stop working if a singlenanotube fails at a single point.

Therefore, though a body of art and literature exists and is evolvingfor the use of individual nanotubes in a sensor arrangement, a needexists for a more reliable vehicle or platform to serve as a sensor.

SUMMARY

The invention relates to one or more sensor platforms and methods ofmaking such platforms wherein sensor platforms include sensor elementsoriented substantially non-horizontally—e.g., substantiallyvertically—with respect to a major surface of a substrate (which isunderstood to be “horizontal”). According to various embodiments of thepresent invention, a sensor element comprises one or more nanostructuressuch as nanotubes. According to certain embodiments, a sensor elementmay have or may be made to have an affinity for a corresponding analyte.

Under certain embodiments, a sensor platform includes a sensor elementhaving a collection of nanotubes with one or more measurable electricalcharacteristics. A support structure supports the sensor element so thatit may be exposed to a fluid, and control circuitry electrically sensesthe electrical characterization of the sensor element so that thepresence of a corresponding analyte may be detected.

Under another embodiment of the invention, a sensor element has anaffinity for the corresponding analyte.

Under another embodiment of the invention, nanotubes used are pristinenanotubes.

Under another embodiment of the invention, nanotubes are derivatized tohave or to increase the affinity.

Under another embodiment of the invention, nanotubes are functionalizedto have or to increase the affinity.

Under another embodiment of the invention, the sensor element has anaffinity for at least two analytes and the plurality of nanotubesincludes at least two types of nanotubes, a first type of nanotubehaving an affinity for a first analyte and a second type of nanotubehaving an affinity for a second analyte.

Under another embodiment of the invention, the support structureincludes a channel and the sensor element is suspended to span thechannel.

Under another embodiment of the invention, the support structureincludes a conductive electrode positioned in the channel, and thesensor element is deflectable in response to the control circuitry tocontact the electrode so that a semiconducting gating effect of thenanotubes in the sensor element may be electrically detected.

Under another embodiment of the invention, an upper electrode ispositioned above and separate from the sensor element.

Under another embodiment of the invention, the sensor platform comprisesa conductive element located apart from the sensor element so that theconductive element and the sensor element are in a capacitiverelationship.

Under another embodiment of the invention, circuitry to measure acapacitance associated with the conductive element and the sensorelement comprises an additional, reference capacitor that in turncomprises one or more nanotubes spaced apart from an additionalconductive element.

Under another embodiment of the invention, the sensor platform comprisesa first conductive element contacting the sensor element at a firstpoint and a second conductive element contacting the sensor element at asecond point, so that an electric current can run through the sensorelement between the first and second conductive elements.

Under another embodiment of the invention, circuitry to measure theresistance between the first and second contacts to the sensor elementcomprises a reference resistor that in turn comprises one or morenanotubes separately contacted by conductive elements.

Under another embodiment of the invention, a large-scale array of sensorplatforms is provided in which the array includes a large plurality ofsensor platform cells.

Under certain embodiments of the invention, a large-scale array ofsensor platforms includes a plurality of sensor elements comprising oneor more nanotubes

According to embodiments of the invention, sensors may be made byproviding a support structure; providing one or more nanotubes on thesupport structure; and providing control circuitry to electrically sensethe electrical characterization of the sensor element so that thepresence of a selected analyte may be detected.

Under another embodiment of the invention, the sensor element has anaffinity for the selected analyte.

Under another embodiment of the invention, the nanotubes are pristinenanotubes.

Under another embodiment of the invention, the nanotubes are derivatizedto have or to increase the affinity.

Under another embodiment of the invention, the nanotubes arefunctionalized to have or to increase the affinity.

Under another embodiment of the invention, a pattern is defined withrespect to a collection of nanotubes on a support structure, whichpattern corresponds to a sensor element; and a portion of the fabric isremoved so that a patterned collection remains on the substrate to formthe sensor element having a collection of at least one nanotube andhaving an electrical characterization.

Under another embodiment of the invention, a collection of nanotubes isformed by growing the collection on the substrate using a catalyst.

Under another embodiment of the invention, during the growing of thenanotube collection, nanotubes are derivatized to have an affinity for acorresponding analyte.

Under another embodiment of the invention, during the growing of thenanotube collection, the nanotubes are functionalized to have anaffinity for a corresponding analyte.

Under another embodiment of the invention, the nanotube collection isformed by depositing a solution of suspended nanotubes on the substrate.

Under another embodiment of the invention, the sensor elements are madeof pre-derivatized nanotubes.

Under another embodiment of the invention, the sensor elements are madeof pre-functionalized nanotubes.

Under another embodiment of the invention, the nanotube collection isderivatized after its growth.

Under another embodiment of the invention, the nanotube collection isfunctionalized after its growth.

Under another embodiment of the invention, the patterned fabricremaining on the substrate is derivatized.

Under another embodiment of the invention, the patterned fabricremaining on the substrate is functionalized.

Under another embodiment of the invention, a conductive element locatedapart from the sensor element is provided so that the conductive elementand the sensor element are in a capacitive relationship.

Under another embodiment of the invention, circuitry to measure acapacitance associated with the conductive element and the sensorelement is provided and, under certain embodiments, comprises anadditional, reference capacitor that itself comprises one or morenanotubes spaced apart from an additional conductive element.

Under another embodiment of the invention, a first conductive elementand a second conductive element are provided such that the firstconductive element contacts the sensor element at a first point and thesecond conductive element contacts the sensor element at a second point,so that an electric current can run through the sensor element betweenthe first and second conductive elements.

Under another embodiment of the invention, circuitry to measure theresistance between the first and second contacts to the sensor elementis provided with a reference resistor that itself comprises one or morenanotubes separately contacted by conductive elements.

Under another embodiment, a sensor element is substantially surroundedby support structure material so that it is not substantially exposed tocontact with fluid that may contain an analyte, and thus may serve as areference element.

BRIEF DESCRIPTION OF THE DRAWINGS

In the Drawings,

FIG. 1 is a scanning electron micrograph showing a fabric of nanotubesconforming to the surface of a substrate such that a portion of thenanotube fabric is oriented substantially perpendicularly to a majorsurface of the substrate.

FIGS. 2(A)-(E) illustrate nanotube fabric sensor devices according tocertain embodiments of the invention;

FIGS. 3(A)-(C) illustrate nanotube fabric sensor devices according tocertain embodiments of the invention;

FIGS. 4(A)-(L) illustrate acts of making vertical nanosensor devicesaccording to certain embodiments of the invention;

FIGS. 5-9 illustrate nanotube fabric sensor devices according to certainembodiments of the invention;

FIGS. 10 and 11 illustrate hybrid technology embodiments of theinvention in which nanosensor arrays use nanotube technology andstandard addressing logic.

FIGS. 12(A)-(B) and 13 illustrate framed or patterned sensing-fabricstructures and methods to create them.

FIG. 14 is a scanning electron micrograph of an array of contact holes,in each of which a sensor element could be located to form a large-scalesensor array.

DETAILED DESCRIPTION

Preferred embodiments of the invention provide a new platform or vehicleto be used in sensors and sensor arrays for biological and/or chemicalsensing. They can be built using conventional semiconductor fabricationtechniques and can leverage existing manufacturing infrastructure andprocesses to create sensors employing carbon nanotubes. Themanufacturing techniques are largely compatible with CMOS processes andcan be conducted at lower temperatures than those for making prior-artnanotube sensing structures. They allow fabrication of a massive numberof sensors on a given chip or wafer that can be integrated with variousforms of control and computational circuitry.

In certain embodiments, sensing elements are oriented substantially“vertically”—i.e., substantially perpendicular to the major surface ofan associated substrate (which is understood to define the “horizontal”direction). Sensing elements may also be oriented “diagonally”—i.e., atorientations between the horizontal and vertical relative to the majorsurface of a substrate.

As will be described in more detail below, preferred embodiments of theinvention use elements made from a fabric of nanotubes (“nanofabrics”),rather than using individual nanotubes as was suggested in prior art.These elements may be derivatized or functionalized as is taught in theart for individual nanotubes. Unlike individual nanotubes, thesenanofabric elements provide a degree of redundancy (e.g., the sensorwill still work even if a given tube in the element is faulty), are moreeasily manufactured, and may be manufactured as parts of large arrays ofsensors with complementary circuitry—for example, by locating sensorelements in each of a plurality of members of an array of contact holeslike that pictured in FIG. 14.

The nanofabric elements may be either unmodified or functionalized sothat they may be used to detect chemical analytes, such as organic andinorganic molecules. In certain embodiments, the chemical analyte may bea biological molecule such as peptides, proteins, or nucleic acids. Thenanofabric may be functionalized, either non-covalently or covalently(e.g., by derivatization) so as to interact specifically with aparticular analyte. The modified or unmodified analyte-sensitivenanofabrics may be incorporated into a nanosensor device for detectionof the corresponding analyte in a sample. Preferred embodiments areunderstood to use the principle that charge transfer between SWNTs andadsorbed molecules changes the nanotube conductance, so as to providenovel nanosensor schemes. Preferred embodiments provide methods andcompositions for the detection of target analytes using changes in theconductivity of nanotube fabric upon binding of the analytes.

Sensors according to certain embodiments of the present invention can beused in a way that allows detection and measurement of differences intheir conductance or other electrical properties before and after thenanotubes are bound to analytes—e.g., by interacting non-covalently orcovalently with a nanotube itself or with a complex consisting of ananotube and a functionalization agent.

The change in the sensor's electrical properties may be measured inconjunction with a gating electrode, disposed below or adjacent to thenanotubes, via a field effect on the semiconducting nanotubes, see,e.g., P. Qi et al., “Toward Large Arrays of Multiplex FunctionalizedCarbon Nanotube Sensors for Highly Sensitive and Selective MolecularDetection,” Nano Lett., vol. 3, no. 3, pp. 347-51 (2003). When changesare detected in this way, it may be preferable to utilize a sensor witha suspended nanofabric structure.

The change in the sensor's electrical properties may also be measuredvia an electromechanical mechanism in which differences betweenswitching voltage with respect to, current through, or resistance of ananofabric element in relation to an underlying electrode is determinedbefore and after the nanofabric is exposed to analytes. Further, thephysical presence of the sensed molecules or species may result indetectable strain on the suspended nanofabric, thereby potentiallyallowing molecular weight of the material to be determined directly. Forexample, as the strain energy changes due to binding of sensedmolecules, a corresponding change in voltage could be measured.

Nanosensors according to certain embodiments of the present inventionare compatible with protocols that substantially prevent non-specificbinding of non-target analytes. For an example of non-specific bindingprevention, see Star et al., “Electronic Detection of Specific ProteinBinding Using Nanotube FET Devices,” Nano Lett., vol. 3, no. 4, pp.459-63 (2003).

The nanofabric sensor of certain embodiments of the present inventionmay be used as an electrode in electrochemical sensors—for example,Clark-type sensors. See Lawrence et al., “A Thin-Layer AmperometricSensor for Hydrogen Sulfide: The Use of Microelectrodes To Achieve aMembrane-Independent Response for Clark-Type Sensors,” Anal. Chem., vol.75, no. 9, pp. 2053-59 (2003).

Exemplary Architectural Sensor Platforms

FIGS. 2(A)-(E) illustrate various embodiments of the invention. As willbe described below, the sensor platforms may provide a vehicle in whicha nanofabric element may be derivatized or functionalized afterfabrication of the platform, but, in some embodiments, thederivatization or functionalization of the nanofabric element may beincorporated into the manufacturing steps of forming the sensorplatform. In FIGS. 2(A)-(E), an individual sensor cell is shown, but, aswill be clear from the description below, the utilization of well-knownsemiconductor manufacturing techniques allows these individual sensorcells to be replicated on a massive scale so that a given chip or wafermay have a very large number of sensors that may be essentiallyidentical to one another. The cells may be organized into massivearrays, small groups, or individual entities. The description focuses onthe architecture and basic platform. Subsequent sections discuss how theproperties of the nanofabric element may be tailored in specific ways toachieve specific desired effects.

The nanofabric element 202 of certain embodiments is formed from anon-woven fabric or layer of matted nanotubes (described in more detailbelow, and also described in incorporated references). Under certainembodiments, the fabric is formed of single-walled carbon nanotubes(SWNTs), but other embodiments may utilize multi-walled carbon nanotubes(MWNTs) or mixtures of single- and multi-walled carbon nanotubes orother nanoscopic elements, such as nanowires. The fabric of certainembodiments is substantially a monolayer of nanotubes with substantiallyconstant porosity. This porosity may be substantially determined by, forexample, the number and density of spin coats, which commonly also playsa principal role in substantially determining the capacitance of aparticular nanofabric.

The sensing parameters of the nanofabric element resemble those ofindividual nanotubes. Thus, the predicted sensing times and switchingvoltages for the nanofabric element should approximate the correspondingtimes and voltages for individual nanotubes. Unlike prior art whichrelies on directed growth or chemical self-assembly of individualnanotubes, preferred embodiments of the present invention utilizefabrication techniques involving thin films and lithography. Suchmethods of fabrication lend themselves to generation of nanotubes andnanotube material over large surfaces, such as wafers 300 mm indiameter. (In contrast, growing individual nanotubes over a distancebeyond the sub-millimeter range is currently unfeasible.) The nanofabricelement should exhibit improved fault tolerances over individualnanotubes, by providing redundancy of conduction pathways throughnanofabric elements. (If an individual nanotube breaks, other tubeswithin the fabric can provide conductive paths, whereas, if a solenanotube were used and broken, the associated nanosensing cell would befaulty.) Moreover, the resistances of nanofabric elements should besignificantly lower than those for individual nanotubes, thus decreasingtheir impedance, since a nanofabric element may be made to have largercross-sectional areas than individual nanotubes.

While typically a monolayer fabric of single-walled nanotubes may bedesirable, for certain applications it may be desirable to havemultilayer fabrics to increase current density or redundancy, or toexploit other mechanical or electrical characteristics of a multilayerfabric. Additionally, for certain applications it may be desirable touse either a monolayer fabric or a multilayer fabric comprisingmulti-walled nanotubes or comprising a mixture of single-walled andmulti-walled nanotubes.

A nanosensor crossbar junction may be formed by a crossing of nanotubesand an electrode. Appropriate application of voltages to such a systemcan result in deflection of the nanotubes toward or away from theelectrode, and, in certain embodiments, can result in a bistablejunction with a pair of “on” or “off” states—states in which thenanotubes are in stable positions of contact (e.g., electrical orphysical) with the electrode or separation from the electrode,respectively.

FIG. 2(A), for example, illustrates an exemplary platform (or sensorcell) 200 in cross-sectional view. Platform 200 includes a nanofabricelement 202 that rests on or is pinned to supports 204 and 206. Theelement is suspended over an electrode 208 by a gap distance 210.

Two states of the nanofabric element 202 are shown with the perspectiveviews of FIGS. 2(B)-(C). FIG. 2(B), for example, shows the platform inan undeflected state, and FIG. 2(C) shows the platform in a deflectedstate in which the nanofabric element has been caused to deflect intocontact with electrode 208. Switching between the states is accomplishedby the application, or removal, of specific voltages across thenanofabric element 202 and one or more of its associated electrodes 208.Switching forces are based, in part, on the interplay of electrostaticattraction and repulsion between the nanofabric article 202 and theelectrode 208. Under certain circumstances, the second state of contactbetween nanofabric and electrode is “volatile”: e.g., the nanofabricmoves into contact with the electrode only when voltage is applied, andreturns to its undeflected state when the voltage is removed. Underdifferent circumstances, the state of contact is “nonvolatile”: e.g., itmay initially result from application of a voltage, but it continuesafter that voltage is removed.

Methods to increase adhesion energies between nanotubes and theelectrode surface can be envisioned, and could involve the use of ionic,covalent, or other forces. These methods can be used to extend the rangeof bistability for nanotube-electrode junctions.

Upon successful completion of the sensing activity, it may be desirableto be able to reset a device in the field. In order to accomplish such areset, it is possible that an electrical pulse able to cause removal ofa sensed molecule from a nanosensor could be provided to clear or zerothe state of the sensor. Necessary voltages could be determined forindividual sensor types specifically or could be part of an overallreset pattern which might simultaneously clear all of the sensors fromtheir states at a particular time. Such a reset feature would allowsensors to become saturated but then to be returned to their originalstate so that the device could be reused. Reusability would reduceoverall cost and maintenance requirements.

Under certain embodiments, the electrode 208 may be used as a referenceor as a field generator involved in measurement. A “reference” electrodecould be used to prevent false positive or false negative readings bycreating a comparison between a “sense” cell and a non-binding cell.

Under certain embodiments, each cell may be read by applying currentsand/or voltages to nanofabric articles 202 and/or the electrode 208. Theelectrical properties of the sensor may then be measured (measuringapparatus is not shown). For example, the nanofabric element 202 maycontact the underlying electrode 208 and remain in contact, in anonvolatile state. As a result, a change in the resistance or otherelectrical properties of the element 202, resulting from analytebinding—for example, a gating effect—may be detected. See P. Qi et al.,“Toward Large Arrays of Multiplex Functionalized Carbon Nanotube Sensorsfor Highly Sensitive and Selective Molecular Detection,” Nano Lett.,vol. 3, no. 3, pp. 347-51 (2003).

In certain embodiments, the support structures 204 and 206 are made fromsilicon nitride (Si₃N₄) and are separated by about 180 nm. Meanwhile,the gap distance 202 is approximately 5-50 nm. Such a 5-50 nm gapdistance is preferred for certain embodiments utilizing nanofabrics madefrom carbon nanotubes, and reflects the specific interplay betweenstrain energy and adhesion energy for the deflected nanotubes. Gapdistances of about 5-50 nm commonly create a platform in which adeflected state is retained in a nonvolatile manner, meaning the element202 will stay deflected even if power is removed from the electrodes.Other gap distances may be preferable for other materials. Larger gapdistances may be used to create volatile behavior, meaning that thedeflected state will be lost when power is interrupted.

The electrode 208 may be made of any suitable electrically conductivematerial and may be arranged in any of a variety of suitable geometries.Certain preferred embodiments utilize n-doped silicon to form such aconductive element, which can be, preferably, no wider than thenanofabric article 202, e.g., about 180 nm in width or less. Otherembodiments utilize metal as conductor. In certain embodiments, theelectrode 208 can be constructed from a nanofabric.

Likewise, the material of the support structures 204 and 206 may be madeof a variety of materials and in various geometries, but certainpreferred embodiments utilize insulating material, silicon nitride, orsilicon oxide, and certain embodiments utilize electronic interconnectsembedded within one support structure or both.

In certain embodiments, the element 202 is held to the insulatingsupport structures by friction. In other embodiments, the nanofabricarticle 202 may be held by other means, such as by anchoring thenanofabric to the support structures using any of a variety oftechniques. Evaporated or spin-coated material such as metals,semiconductors or insulators especially silicon, titanium, siliconoxide, or polyimide can be added to increase the pinning strength. Thefriction interaction can be increased through the use of chemicalinteractions, including covalent bonding through the use of carboncompounds such as pyrenes or other chemically reactive species. See R.J. Chen et al., “Non-covalent Sidewall Functionalization ofSingle-Walled Carbon Nanotubes for Protein Immobilization,” J. Am. Chem.Soc., vol. 123, pp. 3838-39 (2001), and Dai et al., Appl. Phys. Lett.,vol. 77, pp. 3015-17 (2000), for exemplary techniques for pinning andcoating nanotubes by metals. See also WO 01/03208 for discussion of suchtechniques.

Specifically, for example, the nanofabric article 202 may be coupled toanother material by introducing a matrix material into the spacesbetween the nanotubes in a porous nanofabric to form a conductingcomposite junction, as described in the references incorporated above.Electrical and mechanical advantages may be obtained by using suchcomposite junctions and connections. In one example, a conductingmaterial is deposited onto the nanofabric and is allowed to penetrateinto the spaces within the porous nanofabric, thus forming an improvedelectrical connection to the nanofabric and reducing the nanofabricarticle's contact resistance. In another example, an insulating materialis deposited onto the nanofabric and is allowed to penetrate into thespaces within the porous nanofabric, thus forming an improved mechanicalpinning contact that increases strain when the article is bent ordeflected.

FIG. 2(C) illustrates a deflected nanofabric sensing switch according toone embodiment of the invention. The electrode or conductive trace 208is disposed near enough to the suspended portion of the nanofabricelement 202 that the two may contact one another when the nanofabric isdeflected. The electrode 208 may also operate to create a field that canalter the electrical properties of a nearby nanofabric sensor; moreparticularly, the electrode 208 may create a field that alters theproperties of semiconducting nanotubes in a nanosensor cell such as thatof FIG. 2(B). It is therefore an object of certain embodiments of theinvention to create a nanofabric sensor composed substantially orentirely of semiconducting nanotubes disposed adjacent to afield-emitting electrode. See P. Qi et al., “Toward Large Arrays ofMultiplex Functionalized Carbon Nanotube Sensors for Highly Sensitiveand Selective Molecular Detection,” Nano Lett., vol. 3, no. 3, pp.347-51 (2003).

FIG. 2(D) illustrates another nanosensor cell 220. In this embodiment,the electrode 208 of platform 200 is replaced with a nonmetal material222 disposed adjacent to the suspended portion of the nanotube fabric202. Pinning structures 224, mentioned above, are shown explicitly inthis case. Such pinning structures can allow facile electricalconnection to the nanofabric as well as providing support or clamping ofthe nanofabric to the underlying surface 204. Pinning structures wouldbe conductive in many applications, but can be insulating or conductive,depending on the application.

FIG. 2(E) illustrates another nanosensor cell 226. In this embodiment,the nanofabric element 202 is not suspended and instead rests uponsupport material 230. Support material 230, which may also becharacterized as a pinning structure, may be anything consistent withuse as a sensor, including but not limited to metals, alloys, ceramics,semiconductors, plastics, glass etc. Such a pinning structure can allowfacile electrical connection to the nanofabric as well as providingsupport or clamping of the nanofabric to the underlying structure 204. Apinning structure would in many cases be conductive, but can beinsulating or conductive, depending on the application.

FIGS. 3(A)-(C) illustrate another sensor cell and the states such a cellmight achieve. In this cell, the nanofabric element 202 is positionedbetween a lower electrode 304 and upper electrode 306. The electrodes304 and 306 (together with element 202) may be electrically stimulatedto deflect the element 202 toward and away from electrode 304. Forexample, in some embodiments, the element 202 may be caused to deflectbetween the “at rest” state of FIG. 3(A) and the deflected state of FIG.3(B). In certain embodiments, such a deflected state may becharacterized as an “on” state in which the nanofabric-electrodejunction is an electrically conducting, rectifying junction (e.g.,Schottky or PN), which may be sensed as such through either thenanofabric article or the electrode 304, when addressed. In certainembodiments where the cell may be in a third state, as illustrated bystructure 314 of FIG. 3(C), the nanofabric article 202 may be deflectedtoward electrode 306 generating an “on” state different from the “on”state of the previous example (relevant electrical properties may be thesame in both “on” states, but are addressed by different electrodes).

It should be recognized that figures such as FIGS. 3(A)-(C) are notdrawn to scale, and the gap distances 210 in a given cell, for example,need not be equal. In other embodiments, the gap on one side of ananofabric article 202 may be different from that on the other side,potentially to allow various combinations of volatile and nonvolatileswitching behavior. Moreover, inclusion of a third trace in the form ofa release node can add a capacity to use this third trace to reset thecell or to isolate a particular cell. For example, a voltage could beapplied to a third trace to isolate a cell by causing a nanofabricarticle to be held in a particular nonvolatile state.

Furthermore, advantages in increased reliability and defect tolerancecan come from the redundancy permitted by the presence of two conductiveelectrodes 304 and 306. Each of the two conductive electrodes may beseparately used to apply forces to move an electromechanicallyresponsive nanofabric element, and each of the two conductive electrodesmay serve as the “contact” for one of two alternative “on” states. Thus,the failure of one conductive trace may not be fatal to sensor junctionperformance. Among other things, the structures as shown in FIG. 3generally facilitate packaging and distribution, and allownanotube-technology cells to be more easily incorporated into othercircuits and systems such as hybrid circuits. The nature of theelectrical architecture can also facilitate the production of stackablesensor layers and the simplification of various interconnects.

Techniques for Tailoring Characteristics of Nanofabric Element

Monolayer nanofabrics are made from single- or multi-walled nanotubes.The electrical properties of nanofabrics are highly tunable dependingupon concentration of nanotubes within a given fabric. Thesecharacteristics can be controlled. For example, by selecting the properlength and width of a nanotube fabric as well as its porosity, aspecific resistance per square can be measured in a range from 1-1000kOhm/□ up to 1-10 megaOhm/□ depending upon the type of device requiredand its necessary characteristics. Lower resistances may be achieved byshrinking the nanofabric dimensions and placing the nanofabric incontact with metal. Certain devices where the concentration of sensorsmust be higher might require a lower resistance nanofabric.

A more sensitive device (e.g., one that uses fewer nanotubes in thenanofabric) would require fewer binding sites for specific analytes andcould have a higher resistance. Many specific methods of preparing thenanofabric can be envisioned, depending upon the specific sensingrequirements for a particular device. Tuning methods of production, andthe resulting products, to device requirements can be performed by usinga combination of spin coating and photolithography in conjunction withfunctionalization or derivatization as described herein.

Nanofabrics may be created by chemical vapor deposition (CVD) or byapplying prefabricated nanotubes onto a substrate (e.g., spin coating).Various exemplary techniques are described in the incorporated and/orpublished patents and patent applications identified above.

In the event that CVD-grown nanotubes are to be utilized, derivitazationor functionalization of the fabric are straightforward. A CVD-grownnanofabric can be derivatized or functionalized in the same fashion asthe spin-coated fabric. Nanotubes grown by CVD can be doped during thegrowth process with a limited number of materials such as boron,silicon, indium, germanium, phosphorous, arsenic, oxygen, selenium, andother monatomic species using current technologies. After the CVDprocess has been completed, CVD-grown nanotubes can be easily doped withan even wider variety of materials, including many types ofmolecules—for example, chemicals, drugs, DNA, RNA, peptides, orproteins.

The fabrication of nanofabrics by spin coating pre-formed nanotubes isdescribed in the incorporated and/or published patents and patentapplications identified above. Such an approach has advantages overfabrication of nanofabrics by CVD. For example, lower temperatures maybe used for manufacture of the device. This allows more materials to beused as a potential substrate in conjunction with the nanofabricelement. In addition, prefabricated nanotubes may be derivatized orfunctionalized with nearly limitless agents before the nanotubes areapplied to a substrate.

Other techniques for forming the nanofabric may be used as well—e.g.,aerosol application, dipping, or any other appropriate method.

Nanofabric sensors may be comprised of semiconducting nanotubes,metallic nanotubes or both. Investigators have shown that metallicnanotubes may be separated from semiconducting nanotubes byprecipitation. See, e.g., D. Chattopadhyay et al., “A Route for BulkSeparation of Semiconducting from Metallic Single-Walled CarbonNanotubes,” J. Amer. Chem. Soc., vol. 125, pp. 3370-75 (Feb. 22, 2003).It is therefore an aspect of certain embodiments of the presentinvention to create nanofabrics of controlled composition(semiconducting vs. metallic) using this or any other method ofseparation. According to one precipitation method, single-wallednanotubes are acid-treated and then functionalized non-covalently—e.g.,in octadecylamine and tetrahydrofuran—causing metallic species toprecipitate out of solution while leaving semiconducting nanotubes insolution. Either of the separate lots of nanotubes may be used fornanofabric creation once they are separated from one another. Separatednanotubes may be used to create nanofabrics for use as nanosensors withor without functionalization, and such nanotubes may be used inspin-coating applications and other appropriate methods as explainedherein and in incorporated references. Furthermore, the relativeconcentrations of semiconducting and metallic nanotubes may becontrolled. For example, one may create a fabric of approximately 90%semiconducting tubes and 10% metallic nanotubes by mixing a solution of100% semiconducting nanotubes with a solution of unseparated nanotubesto acquire the desired concentration of each type of nanotube. Solutionsof 100% semiconducting tubes may be mixed with solutions of 100%metallic nanotubes as well.

Metallic nanotubes may also be destructively eliminated fromalready-formed nanofabrics by current-induced oxidation, see, e.g., P.G. Collins et al., “Engineering Carbon Nanotubes and Nanotube CircuitsUsing Electrical Breakdown,” Science, vol. 292, pp. 706-09 (2001). It isan aspect of certain embodiments of the present invention to utilize theprotocols set forth in this reference to create a nanofabric and toapply an appropriate voltage to it in order effectively to burn awaymetallic nanotubes. This method will work with nanofabrics that arecreated by CVD or by any other process, such as spin coating, etc.

Once formed, the nanofabric can be patterned by using standardlithography techniques, as described in the incorporated and publishedpatent references. Such lithography techniques allow patterning ofnanofabric by permitting the controlled definition of a region of fabricfor use as a sensor element—for example, in the form of a nanotuberibbon of substantially predetermined dimensions.

Exemplary Types of Sensors that May be Made Using the Sensor Platformsof Preferred Embodiments

A nanosensor can be composed of carbon nanotubes or other highly robustmaterials, including nanowires, that can operate under extremeconditions with no loss of sensitivity. Four general types ofnanosensors have been envisioned:

-   -   pristine nanotubes (i.e., non-functionalized nanotubes)    -   non-covalently functionalized nanotubes    -   covalently derivatized nanotubes    -   a hybrid mixture of above.

1. Non-Functionalized, or Pristine, Nanotubes

The first type of sensor utilizes pristine nanotubes in the nanofabricelement—that is, the nanotubes are non-functionalized nanotubes. Thesurfaces of the nanotubes will adsorb analytes, which can alterelectrical properties of the nanotubes, such as nanotube conductance orcapacitance.

Under this approach, nanotubes may adsorb molecules or species ontotheir surfaces, resulting in a measurable change in electricalcharacteristics, such as a change in conductivity, resistance,capacitance, etc. The change in electrical characteristic(s) may bemeasured directly from the nanotubes themselves via an appropriateelectrical contact.

Nanosensors can be used to detect concentrations of specific, knownmolecules. See L. Valentini et al., “Sensors for Sub-ppm NO₂ GasDetection Based on Carbon Nanotube Thin Films,” Appl. Phys. Lett., vol.82, no. 6, pp. 961-63 (2003). It is therefore an aspect of certainembodiments of the present invention to use nanofabric sensors to detectsuch concentrations.

2.-4. Functionalized Nanotubes

Before nanotubes are applied to a surface to create a nanofabric, theycan be functionalized in solution in order to increase the bonding ofthe tubes to a surface and/or to make possible the bonding of, orinteraction with, analytes. It is therefore an object of certainembodiments of the present invention to functionalize individualnanotubes before they are used to create a nanofabric. It is a furtherobject of certain embodiments of the present invention to use suchfunctionalized nanotubes to create nanosensors, especially by patterningthe nanofabric into specific shapes.

Nanotubes may be functionalized in suspension before they are used tocreate a nanofabric, and such functionalized tubes may be stored in bulkbefore use. Such bulk-functionalized nanotubes may be mixed withpristine nanotubes to generate a partially functionalized nanofabric.More than one variety of functionalized nanotube solutions may becombined to generate mixtures of nanotubes to make mixed-functionalizednanofabrics. This procedure can be repeated to generate nanofabricshaving as many different species of functionalized nanotubes as isdesired for sensing. Thus, one could, for example, functionalize ananotube solution with DNA sequences to sense from a test sample justparticular species of interest, such as those associated only with aspecific virus or solely with specific forms of cancer. An aspect ofcertain embodiments of the present invention is the use of nanosensorsin the detection of specific antigens or major histocompatibilitycomplex (MHC)/antigen complexes from mixtures of fluids to be tested asan early warning sensor of disease or infection.

In another embodiment, nanotubes may be functionalized after nanotubeshave been applied to a substrate in order to create a nanofabric. Inthis case, solution or gas phase functionalization could proceed beforeor after patterning the nanofabrics. This technique would lend itself tomultiple spatially-addressable functionalization events across asurface. For example, one could envision using an inkjet-like process tospray various types of functionalizing agents onto specific regions of asubstrate. Subsequent steps could be used to apply additional functionalgroups in the same or different regions to make nanosensor devices withregionally tailored sensing agents on the same substrate. In this way,many different types of analytes could be sensed by a given array,potentially with each cell sensing for the presence of a differentanalyte.

In yet another embodiment, nanotubes may be functionalized after sensingregions are patterned out of the bulk nanofabric. (See U.S. patentapplication Ser. Nos. 10/341,005, 10/341,055, 10/341,054 and 10/341,130for exemplary details on creating and patterning fabrics.) Uponcompletion of patterning, individual regions can be functionalized toserve as specific sensors. Multiple serial functionalizations ormixtures of functionalizing agents can be used to generate hybridsensors capable of sensing more than one analyte at a time on apatterned nanofabric section or many such sections. This property lendsitself to automation and use with robotics.

Suitable analytes include organic and inorganic molecules, includingbiomolecules. In a preferred embodiment, the target analyte may be

-   -   any environmental pollutant(s), including pesticides,        insecticides, toxins, etc.;    -   a chemical or chemicals, including solvents, polymers, organic        materials, etc.;    -   one or more types of therapeutic molecules, including        therapeutic and abused drugs, antibiotics, etc.;    -   one or more types of biomolecules, including hormones,        cytokines, proteins, lipids, carbohydrates, cellular membrane        antigens and receptors (neural, hormonal, nutrient, and cell        surface receptors) or their ligands, etc;    -   whole cells, including prokaryotic (such as pathogenic bacteria)        and eukaryotic cells, including mammalian tumor cells;    -   viruses, including retroviruses, herpes viruses, adenoviruses,        lentiviruses, etc.; and    -   spores; etc.

For example, potential analyte molecules include nucleic acids,oligonucleotides, nucleosides, and their grammatical equivalents, aswell as any and all modifications and analogs thereof, as understood inthe art—including, for example, amino- or thio-modified nucleosides, andnucleotide molecules with alternate backbones or containing one or morecarboxylic sugars, see, e.g., Beaucage et al., Tetrahedron, vol. 49, no.10, p. 1925 (1993); Jenkins et al., Chem. Soc. Rev., pp. 169-176 (1995).Hence, quite generally, molecules having at least two nucleotidescovalently linked together could be potential analytes. Further, thecategory of potential analytes encompasses both single-stranded anddouble-stranded nucleic acids, as well as nucleic acids containingportions of both double-stranded and single-stranded sequences.Similarly, a potential nucleic-acid analyte could be DNA (includinggenomic or cDNA), RNA, or a hybrid, where the nucleic acid contains anycombination of deoxyribo- and ribo-nucleotides, and any combination ofbases, including uracil, adenine, thymine, cytosine, guanine, inosine,xathanine, hypoxathanine, etc. Mimetic compounds for any of the abovemight also act as potential analytes. In like fashion, potentialanalytes include proteins, oligopeptides, peptides, and their analogs,including proteins containing non-naturally occurring amino acids andamino-acid analogs, and peptidomimetic structures.

One skilled in the art will understand that a large number of analytesmay be detected using embodiments of the present invention. Any targetanalyte for which a binding ligand, described herein, may be made may bedetected using the methods and articles of certain embodiments of theinvention.

Nanoimprint lithography may be used as a method of applyingfunctionalization agents to discrete portions of nanofabric and thus tocreate discrete nanosensors. Such a method is primarily used for makingmassive arrays with sub-100 nm features. Inkjet printing technology maybe used for applying functionalization agents to discrete portions of ananofabric to create separate nanosensors on a given wafer. Inkjetprinting can be used to automate the functionalization of discretenanosensor cells, either by applying functionalization agent tonanofabric cells directly, or by applying functionalized nanotubes tothe area where a cell would reside on a substrate. Inkjet printing is anon-impact, dot-matrix printing technology in which droplets of ink or,in this case, nanotube solutions are “jetted” from a small aperturedirectly to a specified position on a surface or medium to create animage.

Investigators have described a way of immobilizing proteins at specificlocations on nanotubes. See I. Banerjee et al., “Location-SpecificBiological Functionalization on Nanotubes: Attachment to Proteins at theEnds of Nanotubes Using Au Nanocrystal Masks,” Nano Lett., vol. 3, no.3, pp. 283-287 (2003). Certain embodiments of the current inventionutilize the teachings of Banerjee in that nanosensors can be made usingproteins immobilized at the ends of nanotubes to sense for complementaryspecies. According to this method, nanocrystals of gold are applied tothe sidewalls of nanotubes, and avidin is adsorbed onto the entiresurfaces of the nanotubes. A chemical etch procedure is performed toremove the gold nanocrystals and therefore also remove the avidinoverlying the gold nanocrystals, leaving only the avidin attached to theends of the nanotubes. It is therefore an aspect of certain embodimentsof the present invention to fabricate nanosensors using this procedureand to immobilize protein at the ends of nanotubes used in nanosensingcells, articles, and elements.

The sensors should be exposed to analytes, either as a part of a fullyor nearly fully exposed system or as part of an encapsulated systemwhereby analytes are introduced in a controlled way. For example, thenanofabric of a gas sensor may be fully exposed to the air, whereas thenanofabric of a DNA sensor might be encapsulated within a complexmicrofluidic analyte introduction mechanism. With regard to the latter,see PCT publication WO 00/62931, “The Use of Microfluidic systems in theElectrochemical Detection of Target Analytes.” In this PCT document, theinventors describe a sensor system whereby a fluid containing analytesis introduced to a sensing chamber by way of microchannels. Optionalstorage chambers and cell lysing chambers may be connected to the systemby way of other microchannels. It is an object of certain embodiments ofthe present invention to utilize nanofabric sensors in such microfluidicsystems.

Another such microfluidic analyte delivery system is described in U.S.Pat. No. 6,290,839 to Kayyem, wherein a detection surface comprises adetection electrode having a monolayer of conductive oligomers, andoptionally a capture binding ligand capable of binding the targetanalyte. The target analyte directly or indirectly binds to the capturebinding ligand to form a binding complex. The binding complex furthercomprises at least one electron transfer moiety. The presence of theelectron transfer moiety is detected using the detection electrode. Itis therefore an object of certain embodiments of the present inventionto use the nanofabric sensor as the sensing element in the deviceaccording to the '839 patent to Kayyem.

The nanosensor according to certain embodiments of the present inventionmay also be used as a detector according to the principles disclosed inU.S. Pat. No. 6,361,958 to Sheih. Sheih relates to a microfluidic devicewith microchannels that have separated regions that have a member of aspecific binding pair member such as DNA or RNA bound to porous polymerbeads or structures fabricated into the microchannel. Microchannels ofembodiments of the invention are fabricated from plastic and areoperatively associated with a fluid propelling component and detector.It is therefore an aspect of certain embodiments of the presentinvention to incorporate a nanosensing fabric into the system of the'958 patent to Sheih.

The nanosensors according to certain embodiments of the presentinvention may also be used for analyte delivery and detection inconjunction with the nanofluidic channels described in incorporatedreferences.

2. Non-Covalent Functionalization

The second type of sensor utilizes a nanofabric element in whichnanotube surfaces are non-covalently functionalized. This allows forinteraction with a wide variety of cations, anions, metal ions, smallmolecules, DNA, and proteins.

Non-covalent functionalization takes advantage of non-covalent bondingof molecules to the sidewalls of nanotubes with substantial retention ofthe chemical structure and electrical characteristics of the nanotubes.Nanosensing devices can take advantage of such functionalization ofnanotubes to increase, or make possible, bonding of nanotubes to analytemolecules or atoms. Nanofabrics may be non-covalently functionalized byadding pyrenes or other chemicals that are known to bind to nanotubes orgraphite. For example, 1-pyrenebutanoic acid and succinimidyl ester inorganic solvent, such as dimethylformamide or methanol, can be used togenerate a succinimydyl functionalized nanotube. This method takesadvantage of the pyrenyl group's interaction with the sidewalls of thenanotubes while generating succinyl ester groups that are highlyreactive with nucleophilic substitution by primary and secondary aminesfound on the surfaces of most proteins and peptides as well as many drugand pro-drug compounds—where a “pro-drug” is, for example, an inactiveprecursor of a drug that is converted into active form in the body bynormal metabolic processes. This functionalization mechanism is used toimmobilize proteins and a wide variety of other biomolecules onto thesidewalls of SWNTs and to sense specifically for molecules thatconjugate or bind those immobilized molecules preferentially. Forexample, streptavidin may be adsorbed onto a nanotube surface in orderto be used in immunohistochemical sensing. See Chen et al.,“Non-covalent Sidewall Functionalization of Single walled CarbonNanotubes for Protein Immobilization,” J. Am. Chem. Soc., vol. 123, pp.3838-39 (2001). The use of such nanosensors is compatible with analytedetection systems where non-specific binding is prevented. See, e.g.,Star et al., “Electronic Detection of Specific Protein Binding UsingNanotube FET Devices”, Nano Lett., vol. 3, no. 4, pp. 459-63 (2003).

Many methods are known for non-covalently functionalizing nanotubes.See, e.g., J. Kong et al., “Nanotube Molecular Wires as ChemicalSensors,” Science, vol. 287, pp. 622-25 (Jan. 28, 2000); U.S. Pat. No.6,528,020; and U.S. Pat. Appl. No. 2002/0172963 to Kelley et al.,“DNA-Bridged Carbon Nanotube Arrays.” For example, coating of a nanotubewith PMMA (polymethylmethacrylate) has been shown to sensitize thenanotube to NO₂ gas, and gold decoration of a nanotube has been shown tosensitize it to the presence of a thiol vapor, see U.S. Pat. No.6,528,020. In fact, since nanotubes retain similar properties tographitic sheets, nearly any method suitable for non-covalentlyfunctionalizing graphite may be used to functionalize nanotubes.

3. Covalent Functionalization

The third type of sensor utilizes a nanofabric element in which acovalently derivatized nanotube surface allows any of the interactionsabove.

Nanotubes have been functionalized using covalent chemical bondingmethods—e.g., involving diazonium salts. See J. L. Bahr et al.,“Functionalization of Carbon Nanotubes by Electrochemical Reduction ofAryl Diazonium Salts: A Bucky Paper Electrode,” J. Am. Chem. Soc., vol.123, no. 27, pp. 6536-42 (2001); J. L. Bahr et al., “HighlyFunctionalized Carbon Nanotubes Using in Situ Generated DiazoniumCompounds,” Chem. Mater., vol. 13, no. 11, pp. 3823-24 (2001). Otherworkers have used solvent-free methods such as aniline in isoamylnitrate. See, e.g., C. A. Dyke et al., “Solvent-Free Functionalizationof Carbon Nanotubes,” J. Am. Chem. Soc., vol. 125, no. 5, pp. 1156-57(2003). Still others have used oxidative processes to functionalizenanotubes in one-pot reactions, in which all reactions occur in a singlereaction vessel. See, e.g., M. G. C. Kahn et al., “Solubilization ofOxidized Single-Walled Carbon Nanotubes in Organic and Aqueous Solventsthrough Organic Derivatization,” Nano Lett., vol. 2, no. 11, pp. 1215-18(2002). Yet others have covalently bound peptide nucleic acid sequencesto single-walled carbon nanotubes. See, e.g., K. A. Williams et al.,“Carbon nanotubes with DNA Recognition,” Nature, vol. 420, p. 761(2002).

For example, Williams et al., supra, uses an approach to providingcovalently functionalized nanotube nanofabrics in which the uniqueproperties of a nanofabric are combined with the specificmolecular-recognition features of DNA by coupling a nanofabric topeptide nucleic acid (PNA, an uncharged DNA analogue) and hybridizingthese macromolecular wires with complementary DNA. This allows theincorporating of DNA-derivatized nanofabrics into larger electronicdevices by recognition-based assembly, and allows using nanofabrics asprobes in biological systems by sequence-specific attachment. Thetechnique used to couple nanofabrics covalently to PNA involvesultrasonically shortening nanofabric ropes for 1 hour in a 3:1 mixtureof concentrated H₂SO₄ and HNO₃. Subsequent exposure to 1 M HCl producesabundant carboxyl end-groups. This material is then dispersed indimethylformamide (DMF, 99.5%) and incubated for 30 min in 2 mM1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 5 mMN-hydroxysuccinimide (NHS) to form nanofabric-bearing NHS esters. PNAadducts are then formed by reacting this material in DMF for 1 hour withexcess PNA (sequence: NH2-Glu-GTGCTCATGGTG CONH2 (SEQ ID NO: 1), whereGlu is a glutamate amino-acid residue and the central block representsnucleic-acid bases). The PNA-derivatized nanofabric is transferred towater and dispersed in 0.5% aqueous sodium dodecyl sulphate. To examineDNA hybridization to this modified nanofabric, fragments ofdouble-stranded DNA with 12-base-pair, single-stranded “sticky” endsthat were complementary to the PNA sequence were used. These fragmentswere produced by cutting double-stranded DNA with restriction enzymesand ligating the products to single-stranded oligonucleotides. Thissticky DNA was hybridized to the PNA-nanofabric in water, deposited onfreshly cleaved mica with 5 mM MgCl₂. The surface was rinsed and dried.Atomic-force micrographs of the DNA/PNA-nanofabric hybrids may then berecorded. The antisense properties of this derivatized complex may beexploited in biological applications, for example in biosensors.

These methods allow appreciable and measurable functionalization ofnanotubes with specific moieties or sensing agents added directlythrough covalent bonding. In effect, the functionalized nanotube becomesa reactive chemical itself and further chemistry can be performed toyield such diverse species as nanotubes with nanocrystals and inorganiccompounds. See, e.g., S. Banerjee et al., “Functionalization of CarbonNanotubes with a Metal-Containing Molecular Complex,” Nano Lett., vol.2, no. 1, pp. 49-53 (2002); S. Banerjee et al., “Synthesis andCharacterization of Carbon Nanotube-Nanocrystal Heterostructures,” NanoLett., vol. 2, no. 3, pp. 195-200 (2002); S. Banerjee et al.,“Structural Characterization, Optical Properties, and ImprovedSolubility of Carbon Nanotubes Functionalized with Wilkinson'sCatalyst,” J. Am. Chem. Soc., vol. 124, no. 30, pp. 8490-48 (2002).These functionalized-nanotube building blocks can be modified using thewealth of available chemistries to decorate them with groups andmoieties necessary to sense nearly any chemical or biological agentdesired.

As is the case with non-covalently functionalized, covalentlyfunctionalized nanotubes may be used in three ways to createnanosensors. The nanotubes may be functionalized separately and appliedto a substrate, for example, by using a spin coating method or othermethod of application. In another embodiment, the nanofabric may beapplied to a substrate and subsequently covalently functionalized beforepatterning. In yet another embodiment, the nanofabric may befunctionalized after creation and patterning of the nanofabric. Each ofthese three methods lends itself to creation of a nanofabric comprisingone or more types of functionalized nanotubes in the presence or absenceof pristine nanotubes, depending upon the sensor application desired.Upon successful generation of a source of nanotubes containing theproper set of functional moieties, a nanosensor can be fabricated usingvarious methods.

4. Hybrid

The fourth type of sensor uses a mixture of two or three of the previoustypes. By using such a mixture, a hybrid nanosensor is created withmultiple binding-site types potentially able to detect multiple analytesand analyte types. Many different possible compositions ofsurface-functionalized nanotubes can be created before nanotubes areapplied to the substrate, thereby allowing for a mixture of sensingcomponents which can simultaneously screen for discrete analytes.

Methods of Making Exemplary Embodiments

FIGS. 4(A)-(L) collectively illustrate various intermediate structurescreated during an exemplary method for creating a substantially verticalnanosensor, including a nanosensor such as that of FIG. 3(A). The stepsshown are for illustrative purposes. Similar techniques and steps can beused to create other nanosensor structures, including those of FIGS.2(D) and 2(E).

A silicon wafer substrate 400 with an insulating or oxide layer 402 isprovided. Alternatively, the substrate may be made from any materialsuitable for use with lithographic etching and electronics, and theoxide layer can be any suitable insulator. The oxide layer 402 ispreferably a few nanometers in thickness, but could be as much as 1 μmthick. A second layer 404 is deposited on insulating layer 402. Thesecond layer has a top surface 406. Two non-exclusive examples of thematerial from which the second layer 404 can be made are metal orsemiconductor. A cavity 407 is defined in the second layer 404. Thecavity 407 can be created in the second layer 404 by reactive ionetching, and is defined by inner walls 408 and, in certain embodiments,an exposed top surface 410 of insulating layer 402 at the base of thecavity. In certain other embodiments, a portion of second layer 404remains such that the bottom of the cavity 407 is conductive.(Alternatively, as illustrated by FIG. 4(B), an insulating layer 412could be provided to top surface 406 which could then be etched togenerate a cavity.) The cavity 407 can be prefabricated as part of atrench or a via provided as part of preprocessing steps—e.g., as part ofan overall integration scheme in the generation of an electronic device.

A first insulating layer 412 made of silicon nitride or other materialis deposited on top of the exposed top surface 410 and top surface 406to generate top layer 414 of intermediate structure 416 in FIG. 4(B).According to one embodiment, the first insulating layer 412 isselectively etchable over polysilicon, nanotubes, silicon oxide, oranother selected insulator. The first insulating layer 412 can act as asacrificial layer to create a gap between subsequent layers and can bein a non-limiting range of thicknesses on the order of 100 to 200 nm.

Nanotube fabric 418 is applied to intermediate structure 416, formingintermediate structure 420 of FIG. 4(C). As described in referenceslisted and incorporated above, non-limiting methods of applying such afabric that may be used are chemical vapor deposition, spin coating,aerosol application, and dipping.

Like the nanofabric layer pictured in FIG. 1, nanofabric layer 418conforms to the underlying insulating layer 412 and substantiallyfollows the geometry of cavity 407. The resulting structure 420 thusincludes two vertical portions 418A of the nanofabric 418, whichportions are designed to be substantially perpendicular to a majorsurface of substrate 401.

A second insulating layer 422 is applied over nanofabric 418. Protectiveinsulating layer 424, which may be an oxide layer, is deposited on topof second insulating layer 422 having top surface 426, to formintermediate structure 428 of FIG. 4(D). Deposition of protectiveinsulating layer 424 on the sidewalls of the channel is substantiallyavoided. An exemplary but non-limiting thickness of protectiveinsulating layer 424 can be on the order of 100 nm. The optimalthickness may be determined based on the need to protect the layersbelow protective layer 424 from additional etching or deposition steps.A non-exclusive example of the method of application of protectiveinsulating layer 424 is sputtering or high-density plasma deposition ofsilicon dioxide.

A polysilicon layer 430 is deposited on top surface 426 of intermediatestructure 428 of FIG. 4(D), filling the space between walls 408 incavity 407 to give intermediate structure 432 of FIG. 4(E). Polysiliconlayer 430 can be deposited to a height greater than that of top surface426 in order to get at least the proper amount of polysilicon layer intocavity 407, creating an overfilling condition as in intermediatestructure 432. Polysilicon layer 430 may be subsequently planarized toetched polysilicon layer 434 with top surface 426 of oxide layer 424, asillustrated by intermediate structure 436 of FIG. 4(F).

FIG. 4(G) illustrates etched polysilicon layer 434 etched to a firstdepth 438, by any appropriate method. An exemplary method of creatingsuch a depth is by reactive ion etch (“RIE”) and is shown inintermediate structure 440. First depth 438 later helps in thedefinition of one edge of a suspended nanofabric segment. The thicknessof the etched polysilicon layer 434 depends, in part, on the depth ofthe original cavity 407, which, in certain embodiments, may be in arange from 200 nm to 1 micron. For certain applications requiringultrahigh speed electromechanical switching sensors, this depth mightpreferably be below 200 nm. This depth can be reduced using thin filmmanufacturing techniques, as discussed below and in documentsincorporated by reference.

A layer of oxide 442 is deposited on exposed surfaces of intermediatestructure 440 to form intermediate structure 448 of FIG. 4(H). Verticalportions of oxide layer 446 cover trench walls, and horizontal portionsof the oxide layer 444 cover top surfaces of polysilicon layer 434 andprotective layer 424. Horizontal oxide layers 444 are removed—forexample, by oxide spacer etching—leaving intermediate structure 450 ofFIG. 4(I).

FIG. 4(J) illustrates polysilicon layer 434 etched to a second depth452. Second depth 452 may be approximately 50 nm deeper than first depth438. The defined gap 454 allows exposure of regions of second insulatinglayer 422, as shown in intermediate structure 456.

Since nanofabrics are permeable, the regions 412A of first insulatinglayer 412 (see FIG. 4(B)) that are adjacent to the regions of nanotubefabric 418A (see FIG. 4(C)) are removable—for example, by wet etching.Removal of materials from beneath a porous nanofabric has been describedby the present applicants in incorporated references. Suitable wetetching conditions to remove regions of first insulating layer 412 andsecond insulating layer 422 leave a suspended nanofabric 458 havingapproximate vertical height 460 as observed in intermediate structure462 of FIG. 4(K). The wet etching may leave an overhang owing to thenature of isotropic wet etching conditions. Other techniques such as dryetching may be utilized to provide an anisotropic etching step. Indeed,various methods of preparing the described structures exist and theinventors use the foregoing as examples to illustrate the versatility ofsuch methods in providing a suitable nanofabric sensing structure.

Vertical height 460 is defined by the etching procedure. When verticalheight 460 is about 200 nm, the thicknesses of first insulating layer412 and second insulating layer 422 should preferably be approximately20 nm if it is desired to have nanosensing elements have alternatenonvolatile “off” and “on” states. If insulating layer thicknesses togenerate an air gap are instead approximately 50 nm, deflected statesmay instead be volatile.

Structure 462 of FIG. 4(K) may be viewed as “final” structureincorporating two nanosensing elements like that shown in FIG. 2(A).Alternatively, if first insulating layer 412 had been made of a materialnot removed by the process that removed portions of second insulating422, the structure that would have resulted would incorporatenanosensing elements like those of FIG. 2(E).

On the other hand, if a three-trace structure or other structure ofadditional complexity is desired, additional steps are needed. Forexample, as indicated by FIG. 4(L), electrode material 466 may bedeposited in trench 407, leaving gaps 468 between electrode material 466and suspended nanotube fabric 458 as shown in intermediate structure470. The resulting structure 470 has a pair of vertically suspendednanofabric portions 472 surrounded by vertical gaps 474 and 476 oneither side of each vertically-suspended nanofabric portion 472.

Structure 470 thus incorporates two nanosensing elements like that ofFIG. 3(A), and thus may serve as a basis for a pair of bi-state ortri-state switching sensors. (Bi-state cells may be fabricated with thesame elements as tri-state cells, but, in bi-state cells, the gapdistance between the nanofabric and one electrode should preferably begreat enough to prevent nonvolatile contact, but close enough to be usedto switch off an oppositely disposed nonvolatile sensor cell.) Thebehavior of such switching devices is influenced by the strain in thesuspended nanofabric portions and the surrounding gap distances.

It is possible to implement many variations on the “common electrode”configuration of structure 470 (so-called because a single cavityelectrode 466 interacts with both of the two nanosensing elements). Forexample, structure 470 can be split into discrete “left” and “right”sections by a divide running vertically through electrode 466, leavingbi- or tri-state switches that may be independently operated.

In these and other embodiments, the nature of the resulting devices andswitches depends on the construction and arrangement of the electrodesand connections, among other factors. Attention is called to theconstruction of various types of electrodes in the followingembodiments, as an indication of the flexibility of these devices andthe variety of their potential uses. Some devices share commonelectrodes between more than one nanofabric article (e.g., twonanofabric switch elements being influenced by a same shared electrode).Other devices have separate electrodes that control the behavior of thenanofabric. One or more electrodes can be used with each nanofabricarticle to control the article, as discussed, for example, in theincorporated reference entitled “Electromechanical Three-Trace JunctionDevices.”

FIG. 5 illustrates an exemplary structure with subsequent layers ofmetallization. This structure 500 includes electrode interconnect 502and via 504 in contact with nanofabric 418, and a contiguous metalliclayer 404 surrounding the electromechanical switch both laterally andsubjacently. It should be apparent to one skilled in the art that thenanofabric sensor is exposed to the milieu where it senses: althoughthis may appear to be a closed structure, it is not necessarily sobecause areas surrounding the vertical nanosensor can be open to fluidsof many types—for example, via open channels running through thethree-dimensional structure (of which only a cross-section is shown inFIG. 5).

FIG. 6 illustrates another exemplary structure with subsequent layers ofmetallization. This structure 600 is similar to intermediate structure500 in several respects. However, an insulating layer 602 separates theportions of metallic layer 404, and therefore metallic layer 404 doesnot surround the electromechanical sensor elements, substantiallypreventing crosstalk.

FIG. 7 illustrates another exemplary structure with subsequent layers ofmetallization. Structure 700 differs from structure 600 in that thenanofabric layer 418 is not continuous, and there are thus twoindependent sensors 702 and 704, which have substantially no crosstalk.

FIG. 8 also shows an exemplary structure with subsequent layers ofmetallization. Structure 800 differs from structure 700 in that, insteadof a single central electrode, there are two central electrodes 802 and804 separated by insulating layer 806. Intermediate structure 800 hastwo nanosensors, which can be operated or read substantiallyindependently.

FIG. 9 displays an additional exemplary structure with subsequent layersof metallization. Structure 900 is similar to intermediate structures700 and 800, except there is no central electrode at all. In thisembodiment, it is possible for the nanofabric sensors to contactmetallic layer 404 to make a volatile or nonvolatile switch, and it ispossible for the switches to contact one another in a volatile ornonvolatile fashion, depending on further details of the design.

The devices and articles shown in the preceding embodiments are givenfor illustrative purposes only, and other techniques may be used toproduce the same or equivalents thereof. Further, the design of thearticles shown may be varied by substituting different types ofmaterials and geometries, to make yet other embodiments. For example,rather than using metallic electrodes, some embodiments of the presentinvention may employ conductive interconnects made from nanotubes.

Use of additional electrodes can provide extra control of a switchingsensor, non-switching sensor, or device constructed according to thepresent description. For example, FIGS. 3(A)-(C) show a device that hastwo distinct electrodes that can act together to push and/or pull avertical nanofabric section. The gap distances help determine whetherthe devices are volatile or nonvolatile for a given set of parameters.

FIGS. 6 and 7 show devices having three distinct electrodes and therebyproviding extra degrees of freedom (e.g., extra redundancy, extrainformation storage or sensing capability, etc.).

FIG. 8 shows four distinct electrodes, since the center electrode isdivided into two electrodes 802 and 804 by application of divider 806.

On the other hand, FIG. 9 shows two electrodes located on opposite sidesof the channel, and uses top electrode 502 as a third electrode, onehaving a direct electrical connection to nanofabric section 418.

There are other electrode connection locations and geometries possiblethat one skilled in the art would know to create.

Further details regarding one exemplary embodiment of a method forproviding a nanofabric region in contact with electrodes able to be usedfor measurements or detection may be described as follows. Such astructure may be generated, in part, by using two standard photomasks topattern gold contacts to a nanofabric line, which, for example, hasdimensions of about 6 μm in length and 2 μm in width. The nanofabriccontains pristine single-walled carbon nanotubes, and is treated with amixture of 10 wt % polyethyleneglycol (PEG) with an average molecularweight of 25,000 and 10 wt % polyethyleneimine with an average molecularweight of 10,000 in water at room temperature overnight. The actualconcentrations and amount of time required for this step can varydepending upon the size and density of the nanofabric required for thedevice. Also, it is noted that the nanotubes are exposed directly tosolvent and must be handled with care in order to prevent damage to thenanofabric. For this reason, air drying rather than nitrogen blowing wasperformed. The nanotube fabrics could be allowed to dry in an oven withor without oxygen. After thorough rinsing in water, the nanofabric issubjected to a 15 mM solution of biotin-N-hydroxysuccinimide ester atroom temperature overnight. After derivatizing of the free amine groupson the nanofabric overnight, the polymer-coated and biotinylatednanofabric can be tested for sensing capabilities by subjecting it to a2.5 μM solution of streptavidin in 0.01 M phosphate buffered saline (pH7.4) at room temperature. This test can be performed while electricalcontacts are attached as long as the measurement voltage is sufficientlylow. The electrical characteristics of the “pretested” (no streptavidinadded) nanofabric are compared with those of the streptavidin-boundnanofabric to delineate a binding event.

The total concentration of binding moieties can be determined by usingstreptavidin that is bound with gold particles. The particles for agiven area of nanofabric can be counted by SEM or AFM to determine theorder of magnitude sensitivity available within a particular device.Since such derivatization can take place over an entire wafer, it iseasy to generate nanofabric sensors with a very narrow range ofcharacteristic binding concentrations (over 4 orders of magnitude ormore).

The methods of fabrication for the nanotube sensors of certainembodiments of the present invention do not require the use ofsubstrates that can withstand CVD temperatures. However, such substratesmay also be used. The sensors of certain embodiments of the presentinvention are typically composed of nanotube fabrics that compriseredundant conducting nanotubes; these fabrics may be created via CVD, orby room-temperature operations as described herein and in incorporatedreferences. In such a redundant sensor, if one sensing nanotube breaks,the device would remain operable because of the redundant conductiveelements in each sensor. Because the nanosensor described herein can befabricated at room temperature, the use of nearly any substrate,including highly flexible materials and plastics is possible.

Nanosensors according to certain embodiments of the present inventioncan be readily manufactured using standard techniques found in thesemiconductor industry such as spin coating and photolithography. Thefeature size of each nanosensor can be determined by photolithography orby deposition. Because such standard techniques are used in theconstruction of the nanosensors, the overall cost, yield, and array sizecan be larger than sensors created by other known techniques. Nanosensorcells according to certain embodiments of the present invention can beused in massive parallel arrays and can be multiplexed using standardCMOS-compatible sense amplifiers and control logic.

The nanosensors according to certain embodiments of the presentinvention are compatible with high-resolution contact printing methods.See H. Li. et al., “High-resolution Printing with Dendrimers,” NanoLett., vol. 2, no. 4, pp. 347-49 (2002). Patterned nanofabrics may becreated on a substrate (as described below and in incorporatedreferences), and those patterned nanotubes may be transferred via anappropriate contact printing method to a second substrate. Parameterssuch as solubility and binding affinity are important factors to beconsidered in selecting suitable substrates. Alternatively,functionalized, patterned nanotubes may be transferred in the samemanner. And still another alternative that utilizes contract printingtechnology is the application of patterns of functionalization agent tospecific, defined regions on patterned nanofabric—e.g., on differentnanofabric sensor cells.

The inventors contemplate that standard semiconductor testing equipmentcan be used in conjunction with the nanofabric sensors in order todetermine whether analytes are bound to nanofabrics. Examples ofstandard testing equipment include wafer probes.

Nanosensors according to certain embodiments of the present inventioncan be produced on surfaces that can withstand CVD temperatures and alsoon surfaces that may not withstand such a harsh environment—e.g., whenspin coating or aerosol application methods are used to create thenanofabric.

As stated above, the nanotubes of the nanofabric may be derivatized orfunctionalized prior to formation of the nanofabric, subsequent to theformation of the fabric, or subsequent to the patterning of the fabric.In the latter case, for example, the three-dimensional structure mightnot be completely sealed but might instead have open channels wherebythe nanofabric could be subjected to a derivatizing or functionalizingagent.

Note that the electrodes—for example, electrodes 466 and 404 of certainillustrated embodiments of the invention—may themselves be formed ofnanofabric materials. In some embodiments, having a nanofabric ribbon orother nanofabric article in place of a metallic electrode permitsremoval of sacrificial materials from regions beneath or next to theelectrode. Fluid may flow through a nanofabric material disposed aboveor adjacent to a sacrificial layer to remove the sacrificial material.

The devices and articles shown and described in the precedingembodiments are given for illustrative purposes only, and othertechniques may be used to produce the same or equivalents thereof.Furthermore, the articles shown may be modified by the substitution ofother types of materials or the use of different dimensions orgeometries. For example, as described above, rather than using metallicelectrodes, some embodiments of the present invention may employconductive interconnects made from, or comprising, nanotubes. Moreover,using vertically oriented nanofabric articles permits exploitation ofthe smaller dimensions achievable with thin film technology, as opposedto those achievable with the lithographic techniques typically used forhorizontally oriented nanofabric articles. For example, in a structuresuch as that depicted in FIG. 2(A), the electrode 208 may be formedusing thin film techniques, and the dimension T across which nanofabricmay be suspended—in this case, essentially the same as the thickness ofthe electrode 208—may be as little as a few nm thick (e.g., 10-100 nm,or less than 10 nm as technology develops). Gap distances such asdistance 202 of FIG. 2(A) can similarly scale downward with thedevelopment of thin film technology. Consequently, a vertically orientednanofabric sensor created by thin film deposition can be much shorter inlength than horizontally oriented nanofabric devices, such as those inincorporated references.

In order to deliver samples to be examined by the sensor, a microfluidicdelivery system may be utilized. Samples of blood, body fluids,chemicals, and the like may be injected or fed into a microfluidicdelivery system. Such a system could then move material through a systemof microfluidic capillaries and pumps to the sensor site. See, e.g., PCTpublication WO 00/62931, “The Use of Microfluidic systems in theElectrochemical Detection of Target Analytes”.

Certain embodiments of the invention provide a hybrid technology circuit1000, as shown in FIG. 10. A core nanosensor cell array 1004 isconstructed using nanofabric as outlined above, and that core issurrounded by semiconductor circuits forming X and Y address decoders1006 and 1008, X and Y buffers 1010 and 1012, control logic 1014, andoutput buffer 1016. The control circuitry surrounding the nanosensingcore may be used for conventional interfacing functions, includingproviding read currents and sensing output voltages at appropriatetimes. Other embodiments may include various forms of logic to analyzethe outputs at appropriate times.

In certain embodiments, the hybrid circuit 1000 may be formed by using ananotube core (having either just nanosensor cells or nanosensor cellsand addressing logic) and by implementing the surrounding circuitryusing a field-programmable gate array.

In another aspect of certain embodiments of the present invention,analogous to the structure shown in FIG. 10, a gas input means 1102 isutilized in place of the microfluidic separator 1002, as shown instructure 1100 of FIG. 11.

Some of the advantages of the sensors according to certain embodimentsof the present invention include an ability to implement large scaleapplication and integration. In addition, one circuit chip may be usedfor the sensors and for processing of the information from the sensorsand for control of the sensors. This is facilitated by havingCMOS-compatible manufacturing processes. FIG. 14 illustrates thepossibilities for a large-scale array of addressable sensor elements byshowing an array of contact holes in which sensor elements might belocated.

Certain embodiments provide methods for detecting changes in electricalproperties such as nanosensor capacitance or resistance through use of acurrent mirror sensing approach, see, e.g., Baker et al., CMOS CircuitDesign, Layout, and Simulation, pp. 427-33 (1998). Investigators haveshown that electrochemical properties of nanotube bundles and singlecarbon nanotube electrodes are reliable enough that such bundles andindividual tubes can be used as electrodes in capacitors, see J. H. Chenet al., “Electrochemistry of Carbon Nanotubes and their Applications inBatteries and Supercapacitors,” Electrochem. Soc., Proc., vol. 11, p.362 (2001); Y. Tu et al., “Nanoelectrode Arrays Based on Low SiteDensity Aligned Carbon Nanotubes,” Nano Lett., vol. 3, pp. 107-09(2003); and the present inventors have shown that electrical propertiesof single nanotubes are significantly maintained in nanofabrics (seereferences incorporated by reference).

As explained in the incorporated reference “Sensor Platform Using aHorizontally Oriented Nanotube Element” (U.S. patent application Ser.No. 10/844,913), filed on May 12, 2004, sensor cells may be constructedin which nanotube sensor elements are arranged in a capacitiverelationship with one or more other conductive structures, and thestructures and approaches to making such structures described thereincan be readily extended to the vertically oriented sensors and methodsfor providing them described herein. For example, material comprisingnanotube fabric may be arranged so that it is on one side of aninsulating layer (e.g., an Si₃N₄ film), with a conductive pad being onthe opposite side of the insulating layer. In such a formation, thenanotube-fabric material can act as one plate of a capacitor, theconductive pad can act as another plate, and the insulating layer canact as an intervening dielectric layer. Electrical connections andcircuitry may then be provided to allow detection of the associatedcapacitance—for example, before and after exposure to a fluid (gas orliquid) that may carry a capacitance-altering analyte. Alternatively,the material comprising nanotube fabric might be protected from exposureby covering the side opposite the dielectric layer with a secondinsulating layer. The resulting capacitive structure could then be usedto provide a reference capacitance, against which the capacitance of ananalyte-sensitive capacitive structure could be measured.

Similarly, the application “Sensor Platform Using a HorizontallyOriented Nanotube Element” (U.S. patent application Ser. No.10/844,913), filed on May 12, 2004, explains how a sensor cell may beconstructed so that an associated resistance may be measured, and thestructures and approaches to making such structures described thereincan be readily extended to the vertically oriented sensors and methodsfor providing them described herein. Such a resistance cell may beconstructed, for example, by including electrical contacts at two ormore different places on a nanofabric layer. Further electricalconnections and circuitry may then be used to measure the resistanceencountered when current runs through the nanofabric between two of thecontacts. A “reference resistor” might be constructed by encapsulatingthe nanofabric within one or more protective insulating layers.Alternatively, the nanofabric cell could be exposed so that its measuredresistance—and, more particularly, changes therein—might be an indicatorof the presence or passage of an analyte or an analyte-carrying fluid.

Furthermore, techniques like those illustrated in FIGS. 4(A) through4(L) can be used to form framing or partial-covering layers for sensorelements, like those depicted in FIGS. 12(A) and 12(B). Likewise, acombination of covering layers can be used, in combination with a seriesof etching and annealing steps, to create a conducting composite layerthat frames a sensor element, as illustrated in FIG. 13 and as describedmore fully in an analogous context in the incorporated reference,“Sensor Platform Using a Horizontally Oriented Nanotube Element” (U.S.patent application Ser. No. 10/844,913), filed on May 12, 2004.

OTHER EMBODIMENTS

Besides carbon nanotubes, other materials with electronic and mechanicalproperties suitable for electromechanical switching could be envisioned.These materials would have properties similar to carbon nanotubes butwith different and likely reduced tensile strength. For embodimentsdesigned to use or to enable electromechanical switching, the tensilestrain and adhesion energies of the material used in place of carbonnanotubes must fall within a range for bistability of the junction andelectromechanical switching properties within acceptable tolerances.

As one example of a use of materials other than carbon nanotubes, it maybe noted that the fabric of a nanosensing capacitor may be made entirelyof carbon nanotubes, or it may be made from nanowires of variouscomposition—e.g., silicon nanowires—or the fabric may be a composite ofnanotubes and nanowires. The creation of such nanowire and compositefabrics is more fully described in incorporated references such as U.S.provisional patent applications entitled “Patterning of NanoscopicArticles.”

Fluid samples delivered to a sensor element for analyte detection caninclude both liquids and gases, and may include analytes in a variety offorms—for example, as part of particulate matter suspended in a fluid.

Further, certain of the above aspects, such as the hybrid circuits andthe nanotube technology for addressing, are applicable to individualnanotubes (e.g., using directed growth techniques, etc.) or to nanotuberibbons. As used herein, phrases such as “collection of at least onenanotube” or “collection of one or more nanotubes” each generallyencompass a number of one or more nanotubes, and potentially othermatter, without regard to such considerations as whether any particularconstituent or constituents of the collection have a special quality ordistinctiveness, or are arranged in a particular way.

A nanofabric sensor may be used as an electrode in a capacitor.Investigators have shown that electrochemical properties of nanotubebundles and single carbon nanotube electrodes are reliable enough thatsuch bundles and individual tubes can be used as electrodes incapacitors. See J. H. Chen et al., “Electrochemistry of Carbon Nanotubesand their Applications in Batteries and Supercapacitors,” Electrochem.Soc., Proc., vol. 11, p. 362 (2001); Y. Tu et al., “Nanoelectrode ArraysBased on Low Site Density Aligned Carbon Nanotubes,” Nano Lett., vol. 3,no. 1, pp. 107-09 (2003). The present inventors have shown thatelectrical properties of single nanotubes are significantly maintainedin nanofabrics (see incorporated references). It is therefore an objectof certain embodiments of the present invention to use nanofabric as anelectrode in a capacitor for use as a nanosensor.

The gaps of a porous nanofabric are especially helpful when capacitancedifferences are measured, because nanofabric/bound-analyte complexesexhibit different capacitances than the fabric sensor alone, and thecapacitance difference is due in part to the greater surface are of thenanofabric alone, as opposed to the nanofabric with bound analytes.

The term “functionalization,” as used herein, generally includes bothcovalent and non-covalent modifications of nanotubes whereas the term“derivatization” signifies the covalent modification of nanotubes.Hence, functionalization may in certain instances involve non-covalenttransformation of the surface of a nanotube into a form with differentfunctional groups or moieties, and, for example, is meant to encompassany alteration or addition to a nanotube or nanotube surface—includingcovalent derivatization—that creates a product with different physicalor electrical characteristics. Derivatization is indicative of acovalent alteration of the chemical structure of one or more nanotubes,or a portion thereof. In both circumstances, the process can becontrolled such that electrical properties of nanotubes may besubstantially retained. Functional groups can include inorganic atomsand molecules as well as organic molecules. Significant biologicalfunctional groups include peptides, nucleic acids, antigens (includingpolypeptide and non-polypeptide antigens) as well as peptide nucleicacids.

It will be further appreciated that the scope of the present inventionis not limited to the above-described embodiments but rather is definedby the appended claims, and that these claims will encompassmodifications of and improvements to what has been described.

1. A sensor platform, comprising a sensor element comprising a non-wovennanotube fabric and having an electrical characterization; a supportstructure, comprising a substrate, for supporting the sensor element sothat it may be exposed to a fluid, and having a major surface of thesubstrate substantially non-parallel to the sensor element; and controlcircuitry to electrically sense the electrical characterization of thesensor element so that the presence of a corresponding analyte may bedetected.
 2. The sensor platform of claim 1 wherein the sensor elementhas an affinity for the corresponding analyte.
 3. The sensor platform ofclaim 2 wherein the sensor element comprises at least one pristinenanotube.
 4. The sensor platform of claim 2 wherein the sensor elementcomprises at least one nanotube derivatized to have or to increase theaffinity.
 5. The sensor platform of claim 2 wherein the sensor elementcomprises at least one nanotube functionalized to have or to increasethe affinity.
 6. The sensor platform of claim 1 wherein the sensorelement has an affinity for at least two analytes and wherein the sensorelement comprises at least two types of nanotubes, a first type havingan affinity for a first analyte and a second type having an affinity fora second analyte.
 7. The sensor platform of claim 2 wherein the supportstructure includes a channel and wherein the sensor element is suspendedto span the channel.
 8. The sensor platform of claim 7 wherein thesupport structure includes a first conductive electrode positioned, atleast in part, in the channel, and wherein the sensor element isdeflectable in response to the control circuitry to contact theelectrode so that a gating effect of the nanotubes in the sensor elementmay be electrically detected.
 9. The sensor platform of claim 8 furtherincluding a second conductive electrode positioned on a side of thesensor element opposite the first conductive electrode.
 10. The sensorplatform of claim 1 including a fluidic separator in fluid communicationwith the sensor platform to deliver a fluid potentially having theanalyte.
 11. The sensor platform of claim 1 wherein the sensor elementrests flat on a portion of the support structure.
 12. The sensorplatform of claim 1 wherein the sensor element is oriented substantiallyperpendicular to the major surface of the substrate.
 13. The sensorplatform of claim 1 wherein the sensor element is reusable in that,after exposure to the corresponding analyte, the sensor element can besubstantially returned to its pre-exposure state by applying a voltage.14. The sensor platform of claim 1 wherein a conductive element islocated apart from the sensor element to form a structure in which theconductive element and sensor element are in a capacitive relationship.15. The sensor platform of claim 14 wherein the sensor element is on oneside of an insulating layer, and the conductive element is a conductivepad that is on another side of the insulating layer.
 16. The sensorplatform of claim 14 wherein the control circuitry comprisescurrent-mirror circuitry to allow a capacitance associated with thesensor element and the conductive element to be measured.
 17. The sensorplatform of claim 14 wherein the control circuitry comprises a referencecapacitor to allow measurement of a capacitance associated with thesensor element and the conductive element to be measured relative to acapacitance of the reference capacitor.
 18. The sensor platform of claim17 wherein the reference capacitor comprises a second sensor elementincluding a non-woven nanotube fabric and a second conductive element inspaced relation to the second sensor element, so that the second sensorelement and the second conductive element are in a capacitiverelationship.
 19. The sensor platform of claim 1 wherein a firstconductive element contacts the sensor element at a first point and asecond conductive element contacts the sensor element at a second pointso that an electric current can run through the sensor element betweenthe first and second conductive elements.
 20. The sensor platform ofclaim 19 wherein the control circuitry comprises current-mirrorcircuitry to allow a resistance between the first and second contactpoints to be measured.
 21. The sensor platform of claim 19 wherein thecontrol circuitry comprises a reference resistor to allow measurementrelative to the resistance of the reference resistor of the resistancebetween the first and second contact points.
 22. The sensor platform ofclaim 21 wherein the reference resistor comprises a second collection ofnanotubes, and third and fourth conductive elements that contact thesensor element at separate points so that an electric current can runthrough the second collection of nanotubes between the third and fourthconductive elements.
 23. The sensor platform of claim 1, furthercomprising a reference sensor element comprising a non-woven nanotubefabric that is substantially surrounded by support structure material sothat it is not substantially exposed to potential contact with a fluid.24. A large-scale array of sensor platforms wherein the array includes alarge plurality of sensor platform cells, each cell comprising: a sensorelement comprising a non-woven nanotube fabric and having an electricalcharacterization; a support structure for supporting the sensor elementso that it may be exposed to a fluid, and having a major surface of thesubstrate substantially non-parallel to the sensor element; and controlcircuitry to electrically sense the electrical characterization of atleast one sensor element so that the presence of a corresponding analytemay be detected.
 25. The large-scale array of claim 24 wherein thesensor element is oriented substantially perpendicular to the majorsurface of the substrate.